A few months ago I was lying in bed, soon to
drift off to sleep, when I heard a bing on my cell phone - my Mom. In that text
was a link to a New York Times article “Birth Control Pills
Still Linked to Breast Cancer, Study Finds” followed by “??!!??” My eye roll
ensued. A burgeoning Ob-gyn, I was too interested to ignore this, I of course
read the article and couldn’t get back to sleep.
You too may have heard of this major study from Denmark, published this year in the
NEJM, which is making waves in the women’s health community. This study used a
health registry (“Danish Sex hormone registry”) to look at 1.8 million Danish
women ages 15-49, over the course of 11 years, and compare rates of breast
cancer among those who used hormonal contraception with those who didn’t. They
further broke down the groups into specific type of hormonal contraception used
(IUDs, various pill formulations, implants) and duration of use (current use,
recent use, and previous use). They adjusted their results to control for
various factors that may have affected their outcomes, such as age, education,
and parity. They controlled for previous VTE, history of breast cancer and IVF
treatments, by not including these women in the study.
After analyzing the results, they found a
whopping 1 additional case of breast cancer per 7,690 women - in other words, breast cancer risk was 20% higher in
current and recent users of hormonal contraception than in those who had never
used it. The risk seems to be linked
to duration of use. In women who had used hormonal contraception for >= 5
years, the elevated risk of breast cancer seemed to be raised for at least 5
years after discontinuation. Note: the study did not find ANY increased risk in
women who had previously used hormonal birth control for < 5 years.
When
comparing preparations they found that the various combinations of combined
OCPs generally did not vary in their propensity to increase risk of breast
cancer. However, levonorgestrel releasing IUDs seemed to raise breast cancer
risk the same as the use of oral levonorgestrel products.
These statistically significant outcomes are -
at first glance - jaw dropping. We have already established the relationship
between estrogens and breast cancer risk; previous case-controlled studies
showed us associations between OCPS containing high doses of estrogen (doses
higher than the preparations we currently use) and breast cancer. But our
understanding of combined OCPs containing less estrogen, and progestin’s
individual role in the increased risk of breast cancer, is definitely murkier.
We know that adding progestins to postmenopausal
women’s hormone replacement therapy DOES increase the risk of breast cancer,
but what about progestin’s effect on premenopausal women - the group of women
who are using hormonal contraception the most? As Mørch et al. explained, 13% of women ages 15-49 (a total of 140 million women worldwide) rely
on hormonal contraception to keep them safe from pregnancy and to alleviate a
multitude of other ailments (PCOS, endometriosis, acne, etc.). At a glance,
this study is telling us that these women, if using hormonal birth control for
>5 years, have increased their odds of developing breast cancer by 20%.
Furthermore, this study negates our previous understanding that the
relatively lower dose of progestins in the levonorgestrel IUDs as compared to
OCPs (52 mg LNg at placement,
initially releasing 20 mcg/day versus OCP formulas containing doses ranging
from .05 - .15 mg per day) poses a lower
risk of hormonal related side effects (i.e. breast tissue proliferation). This
is a difficult pill to swallow when LARCs such as the Mirena IUD have been
touted by the medical community as the “cadillac” of birth control options,
with extremely high safety, efficacy, and low cost. IUDs provide a non-surgical
option for contraception on par with surgical sterilization, but reversible.
They are the most widely used form of reversible birth control worldwide, and
according to recent statistics are rapidly gaining favor in the US
(from 2002- 2012 US IUD use went from 2 - 12%).
But when we delve a bit deeper into the
results of this study, we must ask some questions: First, is this clinically
relevant? The study appears to hold a lot of statistical power; it’s a large
prospective cohort study, but is it too large? The 1.8 million women in the
study are premenopausal, 15-49 years old - a subgroup of women at a very low
risk of getting cancer in the first place. As NPR put it “A 20% increase of a very small
number is still a very small number.” When we look at studies that are this
large, there are bound to be outliers who develop the disease of interest. And
if the baseline incidence rate is extremely low, this “increase in incidence”
is going to be a big percentage jump.
Second, are the patients studied applicable to
our patient population? The patients looked at were Danish citizens, ages
15-79. They did not mention the racial breakdown of these participants, so one
can only assume that the study reflected Denmark’s relatively homogenous
Scandinavian population. In America - the original melting pot, and a country
approximately 57 x larger than Denmark - can we assume that this population’s
breast cancer incidence reflects ours? This relates to racial breakdown but to
other risk factors as well. While the authors of the study did fully adjust
their data for certain factors such as age, education and parity, they were
unable to control for other important factors, such as breastfeeding, age at
menarche, alcohol consumption and physical activity, all of which we know play
a role in breast cancer risk and absolutely will differ between the U.S. and
Denmark.
Additionally, the question of risks versus
benefits arises. We know that hormonal contraception use decreases the
debilitating symptoms of many female illnesses: endometriosis, fibroids, PCOS,
and primary hypogonadism to name a few. Alternatively, hormonal contraception
has also been proven to decrease the risk of other cancers such as endometrial,
ovarian, and colorectal cancer. Most
importantly, hormonal contraception is among our most reliable form of
pregnancy prevention. The ability to plan pregnancy is a KEY component of
female independence, and a fundamental part of gender equality. Moreover, the
risks of pregnancy are major. Recent studies
examining maternal mortality rate in the United States have shown an increase in
recent years, now reaching 24 deaths per 100,000 live births. Does the
relatively minor increased risk of breast cancer associated with hormonal
contraception use outweigh the potential physical and social burden of
unplanned pregnancy, including death?
Lastly, when considering the larger
implications of this research in the U.S, we must acknowledge that this is terrible political timing. In a
climate where Planned Parenthood’s funding is under threat of extinction, is
this information going to be used as another way to implicate contraception as
“the problem” instead of a solution?
Still, the fear of breast cancer in relation
to hormonal contraception persists. This new information is a piece of a larger
puzzle, something that should be considered when counseling patients on
contraception. Patients deserve to know that there may be a small increased
risk of breast cancer with hormonal contraception, even with progestin
releasing IUDs. Perhaps women with family histories of breast cancer will opt
for non-hormonal contraception such as the Paragard. On a larger scale, perhaps
THIS will be the flame that ignites the fire to start creating safer forms of
hormonal contraception for women, or (gasp) even contraception methods for
men….Oh wait. That will never happen.
Robin Metcalfe-Klaw
DUCOM 2018
- Study
- NPR
- NY times
- https://www.nytimes.com/2017/12/06/health/birth-control-breast-cancer-hormones.html
- Nature review article
- NEJM
- Time
- Up to date
- https://www.uptodate.com/contents/intrauterine-contraception-devices-candidates-and-selection?search=rates%20of%20IUD%20use&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1
